Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

A double-blind randomized placebo-controlled crossover study was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and March 2004 at the outpatient department of a university hospital referral center for chronic fatigue syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 × 10 mg/day, followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual Strength (CIS) and a Visual Analogue Scale (VAS).

Fatigue scores fell significantly during methylphenidate intake in comparison with baseline (mean difference: −0.7, P = .010 for VAS; mean difference: −11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: −1.0, P = .001 for VAS; mean difference: −9.7, P <.0001 for CIS). Concentration disturbances, measured with a VAS improved significantly under methylphenidate treatment compared with baseline (mean difference: −1.3, P <.0001) and compared with placebo (mean difference: −1.1, P <.0001). A clinical significant effect (≥33% improvement or CIS ≤76) on fatigue was achieved in 17% of patients, who were considered responders; on concentration in 22% of patients.

Methylphenidate at a dose of 2 × 10 mg/day is significantly better than placebo in relieving fatigue and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are needed to investigate the long-term effects of this treatment.